Miniaturization continues to play a role of an enabling technology in bioinstrumentation by offering key advantages to research in life sciences and pharmaceuticals. Most importantly, it allows significant reduction of research expense by decreasing the consumption of expensive reagents. Furthermore, it enables the study of proteins and compounds that are rare or too expensive to run at a bulk scale. Miniaturization of assays facilitates the increase in through-put and density of information, and can lead to better data quality and less sample variation in a series of assays.
Efforts on miniaturization in bioinstrumentation have delivered a number of revolutionary tools and opened a new venue in life science and pharmaceutical research. Notably, miniaturization enabled large-scale analysis of biological samples at a lower cost, faster speed and simpler operation, and brought about the era of ‘-omics’. A well-known example of a miniaturized device is a DNA microarray. It allows for a large-scale parallel analysis or reaction of samples in a relatively short time and at a low cost. Efforts are currently taken to miniaturize the commonly used multiwell plate (also called “Micro-Titer Plate®”). By means of automation of sample handling high-throughput screening can be performed. It has been proposed to extend the respective miniaturization approach by disposing drops of cells onto a substrate, so that they are substantially arranged in a monolayer (cf. international application WO 2004/111610).
Another example of a miniaturized device is a lab-on-a-chip microfluidic device. Such a lab-on-a-chip device additionally provides fluid manipulation functions, thus allowing mixing, separation, reaction, analysis, detection and measurement processes. Respective chips may also be combined with the multiwell plate approach, which has for example been carried out in establishing a three-dimensional cell culture system (Torisawa, Y. et al., Biomaterials (2005) 26, 2165-2172, Japanese patent application JP 2005095058). As a further approach in miniaturization, the use of microdroplets in an electric field has been suggested for microscale introduction and mixing of material (Velev, O. D. et al., Nature (2003) 426, 515-516). These microdroplets become charged and move in an electric field by a phenomenon known to those skilled in the art as dielectrophoresis (DEP). In another approach, it has been suggested to apply the principles used in magnetic or optical storage media, by placing cells such as droplets on the non-wettable surface of e.g. a rotating disk (U.S. Pat. No. 6,121,048). Yet a further miniaturization approach is the use of microbeads, e.g. in combinatorial chemistry or on-bead assays. Microbeads can be automatically sorted and dispensed based on their properties such as optical density or fluorescent characteristics.
In order to minimize protein adsorption at the solid-water interface, usually a surface treatment such as a coating is employed. However, achieving reproducibility, consistency and uniformity of differential surface coatings and establishing good quality control are a continuous challenge in the production environment.
Protein adsorption is furthermore not only a problem occurring at solid-water, but also at air-water and, where applicable, oil-water interfaces. Recently, Roach et al. (Anal. Chem. (2005), 77, 785) characterized nonspecific protein adsorption at the aqueous-perfluorocarbon interface, as well as ways to control adsorption. In their work, an aqueous droplet of protein and enzyme was encapsulated by perfluorocarbon liquid containing perfluorocarbon-ethylene glycol surfactants. The perfluorocarbon liquid-aqueous interface minimized non-specific adsorption of fibrinogen and bovine serum albumin at the interface. The activities of ribonuclease A and alkaline phosphatase at nanoliter scale surrounded by the perfluorocarbon-aqueous interface were identical to those at the bulk scale. The interface between perfluorocarbon liquid and aqueous solution, particularly in embodiments where for instance a perfluorocarbon-ethylene glycol surfactant is present, provides a biocompatible surface in addition to minimizing evaporation of the aqueous solution. Perfluorocarbon liquid is known to provide one of the most biocompatible interfaces among water-immiscible liquids.
A further problem in the use of microdevices, particularly during incubation at for instance 37° C., prolonged storage and extended sample preparation using for instance large numbers of multiwell plates for screening purposes is evaporation. Currently used means to overcome this problem are the use of multiwell-plate covers or seal-strips, stacking, the use of closed micochips and the optimization of assay protocols in order to minimize waiting time. Evaporation is of particular practical concern, since it can falsify data if it occurs unevenly across multiwell plates.
Additionally, the freedom and flexibility of liquid handling for addition and mixing of different reagents become limited upon miniaturization. The most common platform for miniaturization is a lab-on-a-chip. In this platform, a reagent is injected through an orifice and transported to a specific chamber or area through a rather long channel. In a lab-on-a-chip device, the fluidic circuit generally needs to be preprogrammed accordingly in advance, and it is inconvenient, if not infeasible, to add a specific reagent to a specific position as needed. In an open-well design, this kind of operation can however be performed by simply placing a dispenser above the desired position and dispensing the reagent. It is therefore desirable to be endued with an open-well design in which it is simple and straightforward to configure dispensing and mixing of reagents in a chip.
Accordingly it is an object of the present invention to provide an apparatus and a method for processing a chemical and/or biological sample which avoids the above discussed disadvantages of a multiwell-plate and lab-on-a-chip device.